title: Role of p300 in regulating neuronal nitric oxide synthase gene expression through nuclear factor-κB-mediated way in neuronal cells.
abstract: Nuclear factor (NF)-κB acetylation has been shown to participate in a number of neurological processes by regulating the expression of certain genes. We have previously demonstrated the neuronal nitric oxide synthase (nNOS) expression and nitric oxide (NO) production may be regulated by NF-κB acetylation via an NF-κB responsive element within the nNOS promoter in neuronal cells. p300 is a ubiquitous transcription coactivator with intrinsic histone acetyltransferase (HAT) activity, which is important in the nervous system. In the present study, we aimed at probing if p300 participated in regulating the nNOS expression through the NF-κB-mediated way. As a result, we found p300 enhanced the nNOS protein and mRNA levels in human neuroblastoma SK-N-SH cells by enhancing the binding of NF-κB to the nNOS promoter and NF-κB-mediated nNOS transcription. Meanwhile, p300 was shown to directly acetylate NF-κB p65 and p50 subunits, interact with NF-κB and bind to the NF-κB responsive element region within the nNOS promoter. Taken together, our results indicate p300 acts as both an HAT and a coactivator in regulating NF-κB-mediated nNOS expression, which provide some correlations between p300 and nNOS in neuronal cell, and suggest that some p300-related neurological disorders may be partially based on its effect on the nNOS expression.
authors.affiliation: Department of Medical Genetics, College of Basic Medical Science, China Medical University, Shenyang 110001, PR China. yhli@mail.cmu.edu.cn
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: C
authors.initials: C
authors.lastname: Li
authors.forename: L
authors.initials: L
authors.lastname: Sun
authors.forename: G
authors.initials: G
authors.lastname: Chu
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: F
authors.initials: F
authors.lastname: Chen
authors.forename: G
authors.initials: G
authors.lastname: Li
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D000107:Acetylation; D045744:Cell Line, Tumor; D050881:E1A-Associated p300 Protein / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I / Q000096:biosynthesis / Q000235:genetics*
chemical_list: D016328:NF-kappa B; D052248:Nitric Oxide Synthase Type I; D050881:E1A-Associated p300 Protein; C494360:EP300 protein, human
keywords: ChIP; EDTA; HAT; NF-κB; NO; PCR; PVDF; SD; SDS–PAGE; acetylation; chromatin immunoprecipitation; eNOS; endothelial nitric oxide synthase; ethylenediaminetetraacetic acid; histone acetyltransferase; iNOS; inducible nitric oxide synthase; nNOS; nervous system; neuronal nitric oxide synthase; nitric oxide; nuclear factor-κB; p300; polymerase chain reaction; polyvinylidene fluoride; sodium dodecyl sulfate–polyacrylamide gel electrophoresis; standard deviation